title: Human cathelicidin LL-37-derived peptide IG-19 confers protection in a murine model of collagen-induced arthritis.
abstract: Current therapies for autoimmune chronic inflammatory diseases e.g. rheumatoid arthritis (RA) include inhibitors of inflammatory cytokines. However, these therapies can result in increased risk of infections. There is a need to explore alternate strategies that can control inflammation without compromising the innate ability to resolve infections. In this study, we examined the effect of small peptides derived from endogenous cathelicidin peptides in a murine model of collagen-induced arthritis (CIA). Cathelicidins are immunomodulatory peptides known to control infections. We demonstrate that the administration of the peptide IG-19, which represents an internal segment of the human cathelicidin LL-37, decreased disease severity and significantly reduced the serum levels of antibodies against collagen type II in the CIA model. IG-19 peptide reduced cellular infiltration in joints, prevented cartilage degradation and suppressed pro-inflammatory cytokines in the CIA mice. We also showed that not all cathelicidin-derived peptides exhibit similar functions. A bovine cathelicidin-derived peptide IDR-1018 did not exhibit the beneficial effects observed with the human cathelicidin LL-37-derived peptide IG-19, in the same murine model of CIA. This is the first study to provide evidence demonstrating the ability of a peptide derived from the human cathelicidin LL-37 to alleviate the arthritic disease process in a murine model of RA. Our results has lead us to propose a new approach for controlling autoimmune chronic inflammatory disorders such as RA, by using specific synthetic derivatives of endogenous host defence peptides. Cathelicidin-derived peptides are particularly attractive for their dual antimicrobial and anti-inflammatory actions.
authors.affiliation: Manitoba Centre for Proteomics and Systems Biology, Department of Internal Medicine, University of Manitoba, Winnipeg, MB, R3E 3P4, Canada.
authors.forename: Leola N Y
authors.initials: LN
authors.lastname: Chow
authors.forename: Ka-Yee Grace
authors.initials: KY
authors.lastname: Choi
authors.forename: Hadeesha
authors.initials: H
authors.lastname: Piyadasa
authors.forename: Maike
authors.initials: M
authors.lastname: Bossert
authors.forename: Jude
authors.initials: J
authors.lastname: Uzonna
authors.forename: Thomas
authors.initials: T
authors.lastname: Klonisch
authors.forename: Neeloffer
authors.initials: N
authors.lastname: Mookherjee
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D023181:Antimicrobial Cationic Peptides / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000628:therapy*; D001172:Arthritis, Rheumatoid / Q000628:therapy; D003094:Collagen / Q000276:immunology; D016207:Cytokines / Q000097:blood* / Q000187:drug effects; D004195:Disease Models, Animal; D007596:Joints; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D054804:Cathelicidins
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D023181:Antimicrobial Cationic Peptides; D016207:Cytokines; D003094:Collagen; D054804:Cathelicidins
keywords: Cathelicidin; Chronic inflammation; Collagen-induced arthritis; Host defence peptides; LL-37; Rheumatoid arthritis